search
Back to results

Blinatumomab Versus Standard of Care Chemotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Primary Purpose

Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Blinatumomab
Standard of Care Chemotherapy
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia focused on measuring Relapsed; Refractory; B-precursor; Acute Lymphoblastic Leukemia; Philadelphia Negative; ALL; Blinatumomab; Leukemia; Standard of Care; SOC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • Subjects with Philadelphia negative B-precursor ALL, with any of the following:

    • refractory to primary induction therapy or refractory to salvage therapy,
    • in untreated first relapse with first remission duration <12 months
    • in untreated second or greater relapse
    • relapse at any time after allogeneic HSCT
  • Subject has received intensive combination chemotherapy for the treatment of ALL for initial treatment or subsequent salvage therapy.
  • Greater than 5% blasts in the bone marrow
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Exclusion Criteria

  • Malignancy other than ALL within 5 years before blinatumomab treatment, except for adequately treated selected cancers without evidence of disease
  • Diagnosis of Burkitt's leukemia according to World Health Organization classification, or human immunodeficiency virus (HIV), Hepatitis B or C, or other clinically significant disorder
  • Current relevant central nervous system (CNS) pathology or known or suspected CNS involvement
  • Isolated extramedullary disease
  • Current autoimmune disease or history of autoimmune disease with potential CNS involvement
  • Autologous HSCT within 6 weeks or allogeneic HSCT within 12 weeks before blinatumomab treatment, or eligibility for allogeneic HSCT at the time of enrollment
  • Active acute grade 2 to 4 graft versus host disease (GvHD) according to Glucksberg et al (1974) criteria that required systemic treatment to prevent or treat GvHD 2 weeks before blinatumomab treatment
  • Known exclusion criteria to investigator choice of SOC chemotherapy (per package insert)
  • Cancer chemotherapy or radiotherapy with 2 weeks, or immunotherapy (included CD19 therapy) within 4 weeks of protocol-specified therapy
  • Abnormal laboratory values (alanine or aspartate transaminase [ALT or AST] or alkaline phosphatase [ALP] ≥ 5 × upper limit of normal [ULN]; total bilirubin or creatinine ≥ 1.5 × ULN), or calculated creatinine clearance < 60 mL/min.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Blinatumomab

Standard of Care Chemotherapy

Arm Description

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab. Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period. The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy. Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Outcomes

Primary Outcome Measures

Overall Survival
Overall survival (OS) was calculated from time of randomization until death due to any cause. Participants still alive were censored at the date they were last known to be alive.

Secondary Outcome Measures

Percentage of Participants With Complete Remission Within 12 Weeks of Treatment Initiation
Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts. Complete Remission (CR) was defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1,000/μl. CR must have occurred within 12 weeks of the first dose of therapy.
Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi) Within 12 Weeks of Treatment Initiation
Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts. Complete remission was defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts: platelets > 100,000/μl, and ANC > 1,000/μl. Complete Remission with partial hematological recovery (CRh*) was defined as ≤ 5% blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl. Complete remission with incomplete hematological recovery (CRi) was defined as ≤ 5% blasts in the bone marrow, no evidence of disease and incomplete recovery of peripheral blood counts: platelets > 100,000/μl or ANC > 1000 (but not both).
Event Free Survival (EFS)
Event free survival was defined as the time from randomization until a documented relapse after achieving CR/CRh*/CRi or death, whichever occurred first. Participants who failed to achieve a CR/CRh*/CRi within 12 weeks of treatment initiation were considered as non-responders and assigned an EFS duration of 1 day. Participants still alive and relapse-free were censored on their last disease assessment date. A relapse event was any one of the following: Hematological relapse: proportion of blasts in bone marrow >5% or blasts in peripheral blood after documented CR or CRh* or CRi Progressive disease: An increase from baseline of at least 25% of bone marrow blasts or an absolute increase of at least 5,000 cells/μL in the number of circulating leukemia cells Extramedullary relapse: extramedullary lesion that is new or increased by 50% from nadir as assessed by Cheson criteria. The Kaplan-Meier estimate of EFS at 6 months is reported.
Duration of Complete Remission
Duration of complete remission, calculated only for participants who achieved a CR, was calculated from the date a CR was first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurred first. Participants who did not have a relapse event were censored on their last disease assessment date.
Duration of Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi)
Duration of CR/CRh*/CRi, calculated only for participants who achieved a CR/CRh*/CRi, was calculated from the date a CR/CRh*/CRi was first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurred first. Participants who did not have a relapse event were censored on their last disease assessment date.
Percentage of Participants With Minimal Residual Disease (MRD) Within 12 Weeks of Treatment Initiation
Bone marrow samples were evaluated for MRD remission by a central laboratory. MRD remission was defined as the occurrence of an MRD level below 10^-4 measured by quantitative reverse transcription polymerase chain reaction (PCR) or flow cytometry.
Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
Number of Participants With Adverse Events
Adverse events (AEs) were graded for severity according to the CTCAE version 4.0, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Treatment-related adverse events (TRAEs) were those assessed by the investigator as possibly related to blinatumomab based on response to the question: Is there a reasonable possibility that the event may have been caused by blinatumomab or other protocol-specified therapies/procedures?
100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant
The analysis of 100-day mortality after allogeneic HSCT was assessed for participants who achieved a best response of CR/CRh*CTi within 12 weeks of treatment initiation, who received an allogeneic HSCT and did not receive any additional anticancer treatment before the transplant. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT. The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive.
Number of Participants With Anti-blinatumomab Antibodies
Anti-blinatumomab binding antibodies were evaluated using a validated electrochemiluminescence (ECL)-based assay (binding assay). Samples positive for binding were analyzed using a cell-based bioassay to determine if the detected antibodies had neutralizing properties (neutralizing assay).
Time to a 10-point Decrease From Baseline in Global Health Status and Quality of Life or Death
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is a 30-item questionnaire that assesses the health related quality of life of cancer patients. The EORTC QLQ-C30 consists of a global health status/quality of life (QoL) scale, 5 functional scales, 3 symptom scales, and 6 single items. The global health/QoL scale consists of 2 questions that ask participants to rate their overall health and overall quality of life durig the past week on a scale from 1 (very poor) to 7 (excellent). The scale score was derived as the sum of each score and transformed to a scale from 0 to 100 where higher scores represent a high QoL. Time to a ≥10-point decrease from baseline GHS/QoL or death, whichever came first, was calculated from baseline. Participants still alive and without a 10-point decrease in GHS/QoL EORTC QLQ-C30 were censored on their last EORTC QLQ-C30 assessment date.

Full Information

First Posted
December 3, 2013
Last Updated
January 4, 2022
Sponsor
Amgen
search

1. Study Identification

Unique Protocol Identification Number
NCT02013167
Brief Title
Blinatumomab Versus Standard of Care Chemotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Official Title
A Phase 3, Randomized, Open Label Study Investigating the Efficacy of the BiTE Antibody Blinatumomab Versus Standard of Care Chemotherapy in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) (TOWER Study)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Terminated
Study Start Date
January 3, 2014 (Actual)
Primary Completion Date
December 29, 2015 (Actual)
Study Completion Date
March 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective was to evaluate the effect of blinatumomab on overall survival when compared to standard of care (SOC) chemotherapy.
Detailed Description
Adults with relapsed/refractory B-cell precursor ALL were randomized in a 2:1 ratio to receive blinatumomab or 1 of 4 pre-specified, investigator-chosen, SOC chemotherapy regimens. Randomization was stratified by age (< 35 years vs ≥ 35 years of age), prior salvage therapy (yes vs no), and prior allogeneic HSCT (yes vs no) as assessed at the time of consent. The study consisted of up to a 3-week screening and pre-phase period, a treatment period consisting of induction with 2 cycles of either blinatumomab or SOC chemotherapy, a consolidation phase of up to 3 additional cycles of protocol-specified therapy, and a maintenance phase for up to an additional 12 months with protocol-specified therapy. A safety follow-up visit 30 days after the last dose of protocol-specified therapy and a long-term follow-up period were included. The long-term follow-up part of the study was discontinued prematurely based on a recommendation from the data monitoring committee (DMC) that the study be stopped for benefit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
Keywords
Relapsed; Refractory; B-precursor; Acute Lymphoblastic Leukemia; Philadelphia Negative; ALL; Blinatumomab; Leukemia; Standard of Care; SOC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
405 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Blinatumomab
Arm Type
Experimental
Arm Description
Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab. Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period. The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.
Arm Title
Standard of Care Chemotherapy
Arm Type
Active Comparator
Arm Description
Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy. Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.
Intervention Type
Drug
Intervention Name(s)
Blinatumomab
Other Intervention Name(s)
Blincyto®, AMG 103, MT103
Intervention Description
Blinatumomab is administered as a continuous intravenous infusion (CIV).
Intervention Type
Drug
Intervention Name(s)
Standard of Care Chemotherapy
Intervention Description
FLAG (fludarabine, cytarabine arabinoside, and granulocyte colony-stimulating factor) ± anthracycline-based regimen (e.g. idarubicin 10 mg/m² days 1 & 3; fludarabine 30 mg/m² days 1-5; cytarabine arabinoside 2 g/m² days 1-5). Patients > 60 years: Idarubicin 5 mg/m² day 1 & 3; fludarabine 20 mg/m² day 1-5; cytarabine arabinoside 1 g/m² day 1-5 HiDAC (high-dose cytarabine arabinoside) - based regimen ≥1 g/m²/day ± anthracycline and/or in combination with other drugs such as native Escherichia coli asparaginase, polyethylene glycol linked to asparaginase (PEG-asparaginase), vinca alkaloids, steroids, etoposide or alkylating agents High-dose methotrexate-based regimen (HDMTX; 500 mg/m² to 3 g/m² infused up to 24 hours) in combination with native E. coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents. Clofarabine as a single agent as recommended in the prescribing information or clofarabine-based regimens with 20 mg/m²/day for up to 5 days.
Primary Outcome Measure Information:
Title
Overall Survival
Description
Overall survival (OS) was calculated from time of randomization until death due to any cause. Participants still alive were censored at the date they were last known to be alive.
Time Frame
From randomization until the data cut-off date of 04 January 2016; median observation time was 11.8 months in the SOC group and 11.7 months in the blinatumomab group.
Secondary Outcome Measure Information:
Title
Percentage of Participants With Complete Remission Within 12 Weeks of Treatment Initiation
Description
Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts. Complete Remission (CR) was defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1,000/μl. CR must have occurred within 12 weeks of the first dose of therapy.
Time Frame
12 weeks
Title
Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi) Within 12 Weeks of Treatment Initiation
Description
Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts. Complete remission was defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts: platelets > 100,000/μl, and ANC > 1,000/μl. Complete Remission with partial hematological recovery (CRh*) was defined as ≤ 5% blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl. Complete remission with incomplete hematological recovery (CRi) was defined as ≤ 5% blasts in the bone marrow, no evidence of disease and incomplete recovery of peripheral blood counts: platelets > 100,000/μl or ANC > 1000 (but not both).
Time Frame
12 weeks
Title
Event Free Survival (EFS)
Description
Event free survival was defined as the time from randomization until a documented relapse after achieving CR/CRh*/CRi or death, whichever occurred first. Participants who failed to achieve a CR/CRh*/CRi within 12 weeks of treatment initiation were considered as non-responders and assigned an EFS duration of 1 day. Participants still alive and relapse-free were censored on their last disease assessment date. A relapse event was any one of the following: Hematological relapse: proportion of blasts in bone marrow >5% or blasts in peripheral blood after documented CR or CRh* or CRi Progressive disease: An increase from baseline of at least 25% of bone marrow blasts or an absolute increase of at least 5,000 cells/μL in the number of circulating leukemia cells Extramedullary relapse: extramedullary lesion that is new or increased by 50% from nadir as assessed by Cheson criteria. The Kaplan-Meier estimate of EFS at 6 months is reported.
Time Frame
6 months
Title
Duration of Complete Remission
Description
Duration of complete remission, calculated only for participants who achieved a CR, was calculated from the date a CR was first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurred first. Participants who did not have a relapse event were censored on their last disease assessment date.
Time Frame
Up to the data cut-off date of 04 January 2016; median observation time was 10.8 months in the SOC group and 7.0 months in the blinatumomab group.
Title
Duration of Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi)
Description
Duration of CR/CRh*/CRi, calculated only for participants who achieved a CR/CRh*/CRi, was calculated from the date a CR/CRh*/CRi was first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurred first. Participants who did not have a relapse event were censored on their last disease assessment date.
Time Frame
Up to the data cut-off date of 04 January 2016; median observation time was 10.8 months in the SOC group and 7.2 months in the blinatumomab group.
Title
Percentage of Participants With Minimal Residual Disease (MRD) Within 12 Weeks of Treatment Initiation
Description
Bone marrow samples were evaluated for MRD remission by a central laboratory. MRD remission was defined as the occurrence of an MRD level below 10^-4 measured by quantitative reverse transcription polymerase chain reaction (PCR) or flow cytometry.
Time Frame
12 weeks
Title
Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
Time Frame
Up to the data cut-off date of 04 January 2016; maximum time on study was 23 months.
Title
Number of Participants With Adverse Events
Description
Adverse events (AEs) were graded for severity according to the CTCAE version 4.0, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Treatment-related adverse events (TRAEs) were those assessed by the investigator as possibly related to blinatumomab based on response to the question: Is there a reasonable possibility that the event may have been caused by blinatumomab or other protocol-specified therapies/procedures?
Time Frame
From first dose of protocol-specified therapy until 30 days after the last dose, up to the data cut-off date of 04 January 2016; median duration of treatment was 5 days in the SOC group and 70 days in the blinatumomab group.
Title
100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant
Description
The analysis of 100-day mortality after allogeneic HSCT was assessed for participants who achieved a best response of CR/CRh*CTi within 12 weeks of treatment initiation, who received an allogeneic HSCT and did not receive any additional anticancer treatment before the transplant. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT. The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive.
Time Frame
100 days, from the date of allogeneic HSCT until the data cut-off date of 04 January 2016
Title
Number of Participants With Anti-blinatumomab Antibodies
Description
Anti-blinatumomab binding antibodies were evaluated using a validated electrochemiluminescence (ECL)-based assay (binding assay). Samples positive for binding were analyzed using a cell-based bioassay to determine if the detected antibodies had neutralizing properties (neutralizing assay).
Time Frame
Samples were collected on day 29 at the end of cycle 2 and 30 days after the last dose of blinatumomab (median duration of treatment was 70 days).
Title
Time to a 10-point Decrease From Baseline in Global Health Status and Quality of Life or Death
Description
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is a 30-item questionnaire that assesses the health related quality of life of cancer patients. The EORTC QLQ-C30 consists of a global health status/quality of life (QoL) scale, 5 functional scales, 3 symptom scales, and 6 single items. The global health/QoL scale consists of 2 questions that ask participants to rate their overall health and overall quality of life durig the past week on a scale from 1 (very poor) to 7 (excellent). The scale score was derived as the sum of each score and transformed to a scale from 0 to 100 where higher scores represent a high QoL. Time to a ≥10-point decrease from baseline GHS/QoL or death, whichever came first, was calculated from baseline. Participants still alive and without a 10-point decrease in GHS/QoL EORTC QLQ-C30 were censored on their last EORTC QLQ-C30 assessment date.
Time Frame
From randomization until the data cut-off date of 04 January 2016; EORTC QLQ-C30 was assessed on day 1, 8, 15, and 29 during cycle 1; days 1, 15, and 29 in cycle 2 and each consolidation cycle, and 30-days following the last dose of drug treatment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Subjects with Philadelphia negative B-precursor ALL, with any of the following: refractory to primary induction therapy or refractory to salvage therapy, in untreated first relapse with first remission duration <12 months in untreated second or greater relapse relapse at any time after allogeneic HSCT Subject has received intensive combination chemotherapy for the treatment of ALL for initial treatment or subsequent salvage therapy. Greater than 5% blasts in the bone marrow Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Exclusion Criteria Malignancy other than ALL within 5 years before blinatumomab treatment, except for adequately treated selected cancers without evidence of disease Diagnosis of Burkitt's leukemia according to World Health Organization classification, or human immunodeficiency virus (HIV), Hepatitis B or C, or other clinically significant disorder Current relevant central nervous system (CNS) pathology or known or suspected CNS involvement Isolated extramedullary disease Current autoimmune disease or history of autoimmune disease with potential CNS involvement Autologous HSCT within 6 weeks or allogeneic HSCT within 12 weeks before blinatumomab treatment, or eligibility for allogeneic HSCT at the time of enrollment Active acute grade 2 to 4 graft versus host disease (GvHD) according to Glucksberg et al (1974) criteria that required systemic treatment to prevent or treat GvHD 2 weeks before blinatumomab treatment Known exclusion criteria to investigator choice of SOC chemotherapy (per package insert) Cancer chemotherapy or radiotherapy with 2 weeks, or immunotherapy (included CD19 therapy) within 4 weeks of protocol-specified therapy Abnormal laboratory values (alanine or aspartate transaminase [ALT or AST] or alkaline phosphatase [ALP] ≥ 5 × upper limit of normal [ULN]; total bilirubin or creatinine ≥ 1.5 × ULN), or calculated creatinine clearance < 60 mL/min.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Research Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29607
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Research Site
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Research Site
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Research Site
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Research Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Research Site
City
Prahran
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Facility Name
Research Site
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6150
Country
Australia
Facility Name
Research Site
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Research Site
City
Wels
ZIP/Postal Code
4600
Country
Austria
Facility Name
Research Site
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Research Site
City
Wien
ZIP/Postal Code
1140
Country
Austria
Facility Name
Research Site
City
Antwerpen
ZIP/Postal Code
2060
Country
Belgium
Facility Name
Research Site
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Research Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Research Site
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Research Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Research Site
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Research Site
City
Plovdiv
ZIP/Postal Code
4000
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1756
Country
Bulgaria
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Research Site
City
Brno
ZIP/Postal Code
625 00
Country
Czechia
Facility Name
Research Site
City
Hradec Kralove
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Research Site
City
Praha 10
ZIP/Postal Code
100 34
Country
Czechia
Facility Name
Research Site
City
Praha 2
ZIP/Postal Code
128 20
Country
Czechia
Facility Name
Research Site
City
Creteil Cedex
ZIP/Postal Code
94010
Country
France
Facility Name
Research Site
City
Le Chesnay
ZIP/Postal Code
78157
Country
France
Facility Name
Research Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Research Site
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
Research Site
City
Pessac Cedex
ZIP/Postal Code
33604
Country
France
Facility Name
Research Site
City
Pierre-Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Research Site
City
Toulouse cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
Research Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Research Site
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Research Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Research Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Research Site
City
Kiel
ZIP/Postal Code
24116
Country
Germany
Facility Name
Research Site
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Research Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Research Site
City
München
ZIP/Postal Code
81377
Country
Germany
Facility Name
Research Site
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Research Site
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Research Site
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Research Site
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Research Site
City
Athens
ZIP/Postal Code
10676
Country
Greece
Facility Name
Research Site
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Research Site
City
Ioannina
ZIP/Postal Code
45110
Country
Greece
Facility Name
Research Site
City
Patra
ZIP/Postal Code
26500
Country
Greece
Facility Name
Research Site
City
Thessaloniki
ZIP/Postal Code
57010
Country
Greece
Facility Name
Research Site
City
Dublin
ZIP/Postal Code
8
Country
Ireland
Facility Name
Research Site
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Research Site
City
Jerusalem
ZIP/Postal Code
91031
Country
Israel
Facility Name
Research Site
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Research Site
City
Petah Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Research Site
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Research Site
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
Research Site
City
Bari
ZIP/Postal Code
70124
Country
Italy
Facility Name
Research Site
City
Bergamo
ZIP/Postal Code
24127
Country
Italy
Facility Name
Research Site
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Research Site
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Facility Name
Research Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Research Site
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Research Site
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Facility Name
Research Site
City
Roma
ZIP/Postal Code
00133
Country
Italy
Facility Name
Research Site
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Research Site
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Research Site
City
Venezia
ZIP/Postal Code
30174
Country
Italy
Facility Name
Research Site
City
Verona
ZIP/Postal Code
37134
Country
Italy
Facility Name
Research Site
City
Busan
ZIP/Postal Code
614-735
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Research Site
City
Mexico City
State/Province
Distrito Federal
ZIP/Postal Code
07760
Country
Mexico
Facility Name
Research Site
City
Monterrey
State/Province
Nuevo León
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Research Site
City
Lublin
ZIP/Postal Code
20-081
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
02-776
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
04-141
Country
Poland
Facility Name
Research Site
City
Wroclaw
ZIP/Postal Code
50-367
Country
Poland
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
Research Site
City
Nizhny Novgorod
ZIP/Postal Code
603126
Country
Russian Federation
Facility Name
Research Site
City
Petrozavodsk
ZIP/Postal Code
185019
Country
Russian Federation
Facility Name
Research Site
City
Saratov
ZIP/Postal Code
410012
Country
Russian Federation
Facility Name
Research Site
City
Oviedo
State/Province
Asturias
ZIP/Postal Code
33011
Country
Spain
Facility Name
Research Site
City
Salamanca
State/Province
Castilla León
ZIP/Postal Code
37007
Country
Spain
Facility Name
Research Site
City
Badalona
State/Province
Cataluña
ZIP/Postal Code
08916
Country
Spain
Facility Name
Research Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46026
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Research Site
City
ChangHua
ZIP/Postal Code
50006
Country
Taiwan
Facility Name
Research Site
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
Research Site
City
Tainan
ZIP/Postal Code
70403
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Research Site
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Research Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Research Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Research Site
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
Facility Name
Research Site
City
Bristol
ZIP/Postal Code
BS2 8ED
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
NW3 2PF
Country
United Kingdom
Facility Name
Research Site
City
Oxford
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom
Facility Name
Research Site
City
Sheffield
ZIP/Postal Code
S10 2JF
Country
United Kingdom
Facility Name
Research Site
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Research Site
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28631497
Citation
Delea TE, Amdahl J, Boyko D, Hagiwara M, Zimmerman ZF, Franklin JL, Cong Z, Hechmati G, Stein A. Cost-effectiveness of blinatumomab versus salvage chemotherapy in relapsed or refractory Philadelphia-chromosome-negative B-precursor acute lymphoblastic leukemia from a US payer perspective. J Med Econ. 2017 Sep;20(9):911-922. doi: 10.1080/13696998.2017.1344127. Epub 2017 Jul 11.
Results Reference
background
PubMed Identifier
28249141
Citation
Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017 Mar 2;376(9):836-847. doi: 10.1056/NEJMoa1609783.
Results Reference
background
PubMed Identifier
30947585
Citation
Dombret H, Topp MS, Schuh AC, Wei AH, Durrant S, Bacon CL, Tran Q, Zimmerman Z, Kantarjian H. Blinatumomab versus chemotherapy in first salvage or in later salvage for B-cell precursor acute lymphoblastic leukemia. Leuk Lymphoma. 2019 Sep;60(9):2214-2222. doi: 10.1080/10428194.2019.1576872. Epub 2019 Apr 5.
Results Reference
background
PubMed Identifier
30645768
Citation
Kuchimanchi M, Zhu M, Clements JD, Doshi S. Exposure-response analysis of blinatumomab in patients with relapsed/refractory acute lymphoblastic leukaemia and comparison with standard of care chemotherapy. Br J Clin Pharmacol. 2019 Apr;85(4):807-817. doi: 10.1111/bcp.13864. Epub 2019 Feb 18.
Results Reference
background
PubMed Identifier
29954814
Citation
Stein AS, Larson RA, Schuh AC, Stevenson W, Lech-Maranda E, Tran Q, Zimmerman Z, Kormany W, Topp MS. Exposure-adjusted adverse events comparing blinatumomab with chemotherapy in advanced acute lymphoblastic leukemia. Blood Adv. 2018 Jul 10;2(13):1522-1531. doi: 10.1182/bloodadvances.2018019034.
Results Reference
background
PubMed Identifier
29739753
Citation
Topp MS, Zimmerman Z, Cannell P, Dombret H, Maertens J, Stein A, Franklin J, Tran Q, Cong Z, Schuh AC. Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab. Blood. 2018 Jun 28;131(26):2906-2914. doi: 10.1182/blood-2017-09-804658. Epub 2018 May 8.
Results Reference
background
PubMed Identifier
34830762
Citation
Kantarjian HM, Zugmaier G, Bruggemann M, Wood BL, Horst HA, Zeng Y, Martinelli G. Impact of Blinatumomab Treatment on Bone Marrow Function in Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Cancers (Basel). 2021 Nov 9;13(22):5607. doi: 10.3390/cancers13225607.
Results Reference
background
PubMed Identifier
35622074
Citation
Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
Results Reference
derived
PubMed Identifier
34161631
Citation
Jabbour E, Patel K, Jain N, Duose D, Luthra R, Short NJ, Zugmaier G, San Lucas A, Velasco K, Tran Q, Zaman F, Konopleva M, Kantarjian H. Impact of Philadelphia chromosome-like alterations on efficacy and safety of blinatumomab in adults with relapsed/refractory acute lymphoblastic leukemia: A post hoc analysis from the phase 3 TOWER study. Am J Hematol. 2021 Oct 1;96(10):E379-E383. doi: 10.1002/ajh.26281. Epub 2021 Jul 7. No abstract available.
Results Reference
derived
PubMed Identifier
33542479
Citation
Wei AH, Ribera JM, Larson RA, Ritchie D, Ghobadi A, Chen Y, Anderson A, Dos Santos CE, Franklin J, Kantarjian H. Biomarkers associated with blinatumomab outcomes in acute lymphoblastic leukemia. Leukemia. 2021 Aug;35(8):2220-2231. doi: 10.1038/s41375-020-01089-x. Epub 2021 Feb 4.
Results Reference
derived
PubMed Identifier
32289160
Citation
Rambaldi A, Huguet F, Zak P, Cannell P, Tran Q, Franklin J, Topp MS. Blinatumomab consolidation and maintenance therapy in adults with relapsed/refractory B-precursor acute lymphoblastic leukemia. Blood Adv. 2020 Apr 14;4(7):1518-1525. doi: 10.1182/bloodadvances.2019000874.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

Blinatumomab Versus Standard of Care Chemotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

We'll reach out to this number within 24 hrs